更新于：2024-11-01

κ opioid receptor x NMDA receptor x μ opioid receptor

更新于：2024-11-01

基本信息

关联

项与 κ opioid receptor x NMDA receptor x μ opioid receptor 相关的药物

Dextromethorphan/Morphine

右美沙芬/吗啡

靶点

NMDA receptor x κ opioid receptor x μ opioid receptor

作用机制

NMDA receptor拮抗剂 [+2]

在研机构-

原研机构

Endo International Plc

在研适应症-

非在研适应症

癌症疼痛

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 κ opioid receptor x NMDA receptor x μ opioid receptor 相关的临床结果

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100 项与 κ opioid receptor x NMDA receptor x μ opioid receptor 相关的转化医学

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0 项与 κ opioid receptor x NMDA receptor x μ opioid receptor 相关的专利（医药）

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项与 κ opioid receptor x NMDA receptor x μ opioid receptor 相关的文献（医药）

2023-06-01·Biological Psychiatry

Mu Opioid Receptor Activation Mediates (S)-ketamine Reinforcement in Rats: Implications for Abuse Liability

Article

作者: Gomez, Juan L ; Bonaventura, Jordi ; Shaham, Yavin ; Rizzo, Arianna ; Carlton, Meghan L ; Levinstein, Marjorie R ; Airan, Raag D ; Michaelides, Michael ; Di Ianni, Tommaso ; Ventriglia, Emilya N ; Zarate, Carlos A ; Budinich, Reece C

BACKGROUND(S)-ketamine is an NMDA receptor antagonist, but it also binds to and activates mu opioid receptors (MORs) and kappa opioid receptors in vitro. However, the extent to which these receptors contribute to (S)-ketamine's in vivo pharmacology is unknown.METHODSWe investigated the extent to which (S)-ketamine interacts with opioid receptors in rats by combining in vitro and in vivo pharmacological approaches, in vivo molecular and functional imaging, and behavioral procedures relevant to human abuse liability.RESULTSWe found that the preferential opioid receptor antagonist naltrexone decreased (S)-ketamine self-administration and (S)-ketamine-induced activation of the nucleus accumbens, a key brain reward region. A single reinforcing dose of (S)-ketamine occupied brain MORs in vivo, and repeated doses decreased MOR density and activity and decreased heroin reinforcement without producing changes in NMDA receptor or kappa opioid receptor density.CONCLUSIONSThese results suggest that (S)-ketamine's abuse liability in humans is mediated in part by brain MORs.

2016-05-01·Alcoholism: Clinical and Experimental Research3区 · 医学

Gene Expression Changes in Glutamate and GABA-A Receptors, Neuropeptides, Ion Channels, and Cholesterol Synthesis in the Periaqueductal Gray Following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats

3区 · 医学

Article

作者: Bell, Richard L. ; McClintick, Jeanette N. ; Xuei, Xiaoling ; Edenberg, Howard J. ; McBride, William J. ; Ding, Zheng-Ming ; Liu, Yunlong

BACKGROUNDBinge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including increased pain, fear, and anxiety. The periaqueductal gray (PAG) is involved in processing pain, fear, and anxiety. The effects of adolescent binge drinking on gene expression in this region have yet to be studied.METHODSMale adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking (three 1-hour sessions/d during the dark/cycle, 5 days/wk for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 to 3 g/kg/session). We used RNA sequencing to assess the effects of ethanol intake on gene expression.RESULTSEthanol significantly altered the expression of 1,670 of the 12,123 detected genes: 877 (53%) decreased. In the glutamate system, 23 genes were found to be altered, including reduction in 7 of 10 genes for metabotropic and NMDA receptors. Subunit changes in the NMDA receptor may make it less sensitive to ethanol. Changes in GABAA genes would most likely increase the ability of the PAG to produce tonic inhibition. Five serotonin receptor genes, 6 acetylcholine receptor genes, and 4 glycine receptor genes showed decreased expression in the alcohol-drinking rats. Opioid genes (e.g., Oprk1, Oprm1) and genes for neuropeptides linked to anxiety and panic behaviors (e.g., Npy1r) had mostly decreased expression. Genes for 27 potassium, 10 sodium, and 5 calcium ion channels were found to be differentially expressed. Nine genes in the cholesterol synthesis pathway had decreased expression, including Hmgcr, encoding the rate-limiting enzyme. Genes involved in the production of myelin also had decreased expression.CONCLUSIONSThe results demonstrate that binge alcohol drinking during adolescence produces developmental changes in the expression of key genes within the PAG; many of these changes point to increased susceptibility to pain, fear, and anxiety, which could contribute to excessive drinking to relieve these negative effects.

2007-01-01·European Journal of Pharmacology3区 · 医学

Paradoxical hyperalgesia induced by μ-opioid receptor agonist endomorphin-2, but not endomorphin-1, microinjected into the centromedial amygdala of the rat

3区 · 医学

Article

作者: Leon F. Tseng ; Emma Schwasinger ; Maia Terashvili ; Hsiang-En Wu

The effects of endomorphin-2 or endomorphin-1 microinjected into the centromedial amygdala on the thermally-induced tail-flick response were studied in male CD rats. Microinjection of endomorphin-2 (8.7-35.0 nmol) given into the centromedial amygdala time- and dose-dependently decreased the tail-flick latencies. On the other hand, endomorphin-1 (8-32.6 nmol) given into the same site did not cause any change of the tail-flick latency. However, endomorphin-1 (32.6 nmol) or endomorphin-2 (35.0 nmol) given into the basolateral site of amygdala did not affect the tail-flick latency. Pretreatment with the antiserum against dynorphin A(1-17) (200 microg) significantly reversed the decrease of the tail-flick latency induced by endomorphin-2. The decrease of the tail-flick latency induced by endomorphin-2 was also blocked by the endomorphin-2 selective micro-opioid receptor antagonist 3-methoxynaltrexone (6.4 pmol) and by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (30 nmol), but not by the kappa-opioid receptor antagonist nor-binaltorphimine (6.6 nmol). It is concluded that endomorphin-2, but not endomorphin-1, given into the centromedial amygdala stimulates a 3-methoxynaltrexone-sensitive mu-opioid receptor subtype to induce the release of dynorphin A(1-17), which then acts on the NMDA receptor, but not kappa-opioid receptor for producing hyperalgesia. This conclusion is further supported by the additional findings that dynorphin A(1-17) (2.3 nmol) given into the centromedial amygdala also caused the decrease of the tail-flick latency, which was similarly blocked by the NMDA receptor antagonist MK-801 (30 nmol), but not kappa-opioid receptor antagonist nor-binaltorphimine (6.6 nmol).